Regulatory T Cells Contributes to the Development of Cutting Edge: The Foxp3 Target miR-155
Regulatory T Cells Contributes to the Development of Cutting Edge: The Foxp3 Target miR-155
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发表时间：
2009
期刊：
影响因子：
3.9
通讯作者：
S. Kohlhaas;O. Garden;C. Scudamore;M. Turner;K. Okkenhaug;E. Vigorito
中科院分区：
文献类型：
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作者：
S. Kohlhaas;O. Garden;C. Scudamore;M. Turner;K. Okkenhaug;E. Vigorito
Foxp 3是一种转录因子，对调节性T细胞（TCFs）的正常发育至关重要。在缺乏microRNA（miRNAs）的情况下，Foxp 3（cid：1）TcR发展但不能维持免疫稳态，导致皮屑样疾病。对Foxp 3调控的基因网络的全球分析已经确定了在TcB中高度表达的miRNA miR-155作为Foxp 3的直接靶点。在这项研究中，我们报告了miR-155缺陷小鼠由于发育受损，胸腺和外周中的TcR数量减少。然而，我们没有发现miR-155缺陷型TcR在体外或体内具有缺陷抑制活性的证据。我们的研究结果表明，miR-155有助于Treg的发育，但其他miRNA控制Treg功能。免疫学杂志，2009，182：2578-2582.体内抑制测定通过在FACSAria流式细胞仪上进行细胞分选来分离CD 4（cid：1）CD 25（cid：1）和CD 4（cid：1）CD 45 RB高细胞，产生纯度为（cid：4）99%的群体。使用已发表的结肠炎过继转移模型，将5（cid：3）10 5个CD 45 RB高T细胞单独或与1（cid：3）10 5个野生型或bic/miR-155缺陷型CD 4（cid：1）CD 25（cid：1）细胞一起注射到Rag 2（cid：2）/（cid：2）受体中（17）。通过O.A.G.对注射后12周内结肠炎的严重程度进行独立评分。和CS根据先前公布的标准（18），并给出一致性得分。
Foxp3 is a transcription factor that is essential for the normal development of regulatory T cells (Tregs). In the absence of microRNAs (miRNAs), Foxp3 (cid:1) Tregs develop but fail to maintain immune homeostasis, leading to a scurfy-like disease. Global analysis of the network of genes regulated by Foxp3 has identified the miRNA miR-155, which is highly expressed in Tregs, as a direct target of Foxp3. In this study we report that miR-155-deficient mice have reduced numbers of Tregs, both in the thymus and periphery, due to impaired development. However, we found no evidence for defective suppressor activity of miR-155-deficient Tregs, either in vitro or in vivo. Our results indicate that miR-155 contributes to Treg development, but that additional miRNAs control Treg function. The Journal of Immunology, 2009, 182: 2578–2582. suppression assay in vivo CD4 (cid:1) CD25 (cid:1) and CD4 (cid:1) CD45RB high cells were isolated by cell sorting on a FACSAria flow cytometer, yielding populations of (cid:4) 99% purity. A published adoptive transfer model of colitis was used, injecting 5 (cid:3) 10 5 CD45RB high T cells alone or together with 1 (cid:3) 10 5 wild-type or bic/miR-155-deficient CD4 (cid:1) CD25 (cid:1) cells into Rag2 (cid:2) / (cid:2) recipients (17). The severity of colitis up to 12 wk after injection was independently scored by O.A.G. and C.S., according to previously published criteria (18), and consensus scores are presented.